FDA Approves MAGE-A4 IHC 1F9 pharmDx as Diagnostic Tool in Patients With Synovial Sarcoma
The diagnostic tool can aid the identification of patients with synovial sarcoma who may be eligible for treatment with newly approved afamitresgene autoleucel.
Updated at 11:10 am on August 2, 2024.
The FDA has approved melanoma-associated antigen A4 (MAGE-A4) immunohistochemistry (IHC) 1F9 pharmDx (SK032; Agilent Technologies) as a diagnostic tool to aid in identifying patients who have synovial sarcoma and may be eligible for treatment with the newly approved MAGE-A4-directed engineered T-cell receptor (TCR) T-cell therapy afamitresgene autoleucel (afami-cel, Tecelra; Adaptimmune). The diagnostic tool is the first in vitro diagnostic for MAGE-A4 that is available on the market.1
Image credit: B-design | stock.adobe.com
MAGE-A4 is a cancer testis antigen that is overexpressed in various cancers, such as synovial sarcoma. MAGE-A4 IHC 1F9 pharmDx is an IHC assay that is used to detect the expression of MAGE-A4 in formalin-fixed paraffin-embedded (FFPE) synovial sarcoma tissue. Additionally, MAGE-A4 positivity is a biomarker of eligibility for treatment with afami-cel in hose with synovial sarcoma.1
Further, afami-cel was also approved by the FDA for the treatment of adults with unresectable or metastatic synovial sarcoma who have received prior chemotherapy, are positive with the A*02:01P, A*02:02P, A*02:03P, or A*02:06P HLA antigens, and whose tumor expresses the MAGE-A4 antigen determined by the authorized companion devices, such as MAGE-A4 IHC 1F9 pharmDx. The treatment is a prescription medicine and the first FDA-approved engineered TCR T-cell therapy for a solid tumor cancer.1,2
In a study published in Molecular Therapy Methods and Clinical Development that assessed the eligibility rate for TCR T-cell therapies based on different biomarker screening methods, MAGE-A4 IHC demonstrated efficacy, and its precision was validated. In the study, an anti-MAGE-A4 antibody (clone OTI1F9) showed specific staining of MAGE-A4 without cross-reactivity to MAGE-A1, -A2, -A3, -A6, -A9 (in MAGE-A-transduced NAML6 cell lines), -A10 (in the Mel526 cell line with endogenous high MAGE-A10 expression), and -A11 and -A12 (in Mel624). The anti-MAGE-A4 antibody demonstrated a rate staining (0.28%) to MAGE-A8-transduced MALN6 cell line—which is a high MAGE-A8 expression in approximately 56% of cells—as well as minor cross-reactivity to MAGE-A10-transduced NALM6 cell line, artificial systems that have extremely high MAGE-A8 or MAGE-A10 expression.3
According to the analytical validation, the tumor and tissue samples included showed different MAGE-A4 prevalence in a broad range of solid tumors, but not in normal tissues with the exception of testis and placenta. Additionally, the precision of the MAGE-A4 IHC clinical trial assay was validated at the cutoff (≥30% at ≥2+ intensity) with an 80% and higher inter-run and intra-run concordance, which was mostly 90% and higher. In addition, inter-lab assay transfer demonstrated 100% concordance on a series of samples of multiple indications. Further, pathologists’ scoring demonstrated 80% or higher (mostly ≥90%) intra-reader and inter-reader concordance for a series of samples of multiple indications. The results also demonstrated that accuracy evaluations indicated high reliability when assessing eligibility for clinical trials investigation afami-cel and uzatresgene autoleucel (uza-cel; Adaptimmune).3
“MAGE-A4 plays a significant role in cancer research and holds promise as a therapeutic target. The FDA’s approval of Agilent’s MAGE-A4 IHC 1F9 pharmDx will expand treatment options for individuals diagnosed with synovial sarcoma,” said Lou Welebob, vice president and general manager of Agilent’s Pathology Division, in a news release. “This endorsement amplifies Agilent’s pioneering role in shaping companion diagnostics for groundbreaking cancer therapies.”1
